\ BIP! Finder for COVID-19 - Impact-based ranking

BIP! Finder for COVID-19

This version of BIP! Finder aims to ease the exploration of COVID-19-related literature by enabling ranking articles based on various impact metrics.

Last Update: 18 - 01 - 2023 (628506 entries)

Provided impact measures:
Popularity: Citation-based measure reflecting the current impact.
Influence: Citation-based measure reflecting the total impact.
Reader Attention: The current number of Mendeley readers.
Social Media Attention: The number of recent tweets related to this article.
*More details on these impact measures can be found here.
Score interpretations:
Exceptional score (in top 0.01%).
Substantial score (in top 1%).
Average score (in bottom 99%).
Score not available.
Main data sources:
CORD-19 dataset(1) (list of papers)
LitCovid hub(2) (list of papers)
PMC & PubMed (citations)
Mendeley (number of readers)
COVID-19-TweetIDs(3) (tweets)

Use:  Impact  Relevance & Impact
TitleVenueYearImpactSource
751Coronavirus-19 induces acute severe lung inflammation via IL-1 causing cytokine storm in COVID-19: a promising inhibitory strategy  

N/A

J Biol Regul Homeost Agents2020       LitCov and CORD-19
752Clinical Features and Chest CT Manifestations of COVID-19 in a Single-Center Study in Shanghai, China  

N/A

AJR Am J Roentgenol2020       LitCov and CORD-19
753The perspective of Canadian Healthcare professionals on abortion service during the COVID-19 pandemic  

BACKGROUND: The COVID-19 pandemic and pandemic response created novel challenges for abortion services. Canada was uniquely positioned to transition to telemedicine because internationally common restrictions on abortion medication were removed before the pandemic. OBJECTIVE: We sought to characterize the experiences of abortion health care professionals in Canada during the COVID-19 pandemic and the impact of the pandemic response on abortion services. METHODS: We conducted a sequential mixed methods study between July 2020 and January 2021. We invited physicians, nurse practitioners and administrators to participate in a cross-sectional survey containing an open-ended question about the impact of the pandemic response on abortion care. We employed an inductive codebook thematic analysis, which informed the development of a second, primarily quantitative survey. RESULTS: Our initial survey had 307 respondents and our second had 78. Fifty-three percent were family physicians. Our first survey found respondents considered abortion access essential. We identified three key topicss: access to abortion care was often maintained despite pandemic-related challenges (e.g. difficulty obtaining tests, additional costs); change of practice to low-touch medication abortion care and provider perceptions of patient experience, including shifting demand, telemedicine acceptability and increased rural access. The second survey indicated uptake of telemedicine medication abortion among 89% of participants except in Quebec, where regulations meant procedures were nearly exclusively surgical. Restrictions did not delay care according to 76% of participants. CONCLUSIONS: Canadian health care professionals report their facilities deemed abortion an essential service. Provinces and territories, except Quebec, described a robust pandemic transition to telemedicine to ensure access to services. PODCAST: An accompanying podcast is available in the Supplementary Data, in which the authors Dr Madeleine Ennis and Kate Wahl discuss their research on how family planning care and access to abortion services have changed during the COVID-19 pandemic.

Fam Pract2021       LitCov and CORD-19
754A Review of COVID-19  

There is a new public health crises threatening the world with the emergence and spread of 2019 novel coronavirus (2019-nCoV) or the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The virus originated in bats and was transmitted to humans through yet unknown intermediary animals in Wuhan, Hubei province, China in December 2019. There have been around 96,000 reported cases of coronavirus disease 2019 (COVID-2019) and 3300 reported deaths to date (05/03/2020). The disease is transmitted by inhalation or contact with infected droplets and the incubation period ranges from 2 to 14 d. The symptoms are usually fever, cough, sore throat, breathlessness, fatigue, malaise among others. The disease is mild in most people; in some (usually the elderly and those with comorbidities), it may progress to pneumonia, acute respiratory distress syndrome (ARDS) and multi organ dysfunction. Many people are asymptomatic. The case fatality rate is estimated to range from 2 to 3%. Diagnosis is by demonstration of the virus in respiratory secretions by special molecular tests. Common laboratory findings include normal/ low white cell counts with elevated C-reactive protein (CRP). The computerized tomographic chest scan is usually abnormal even in those with no symptoms or mild disease. Treatment is essentially supportive; role of antiviral agents is yet to be established. Prevention entails home isolation of suspected cases and those with mild illnesses and strict infection control measures at hospitals that include contact and droplet precautions. The virus spreads faster than its two ancestors the SARS-CoV and Middle East respiratory syndrome coronavirus (MERS-CoV), but has lower fatality. The global impact of this new epidemic is yet uncertain.

Indian J Pediatr2020       LitCov and CORD-19
755Wet markets-a continuing source of severe acute respiratory syndrome and influenza?  

CONTEXT: Live-animal markets (wet markets) provide a source of vertebrate and invertebrate animals for customers in tropical and subtropical regions of the world. Wet markets sell live poultry, fish, reptiles, and mammals of every kind. Live-poultry markets (mostly chicken, pigeon, quail, ducks, geese, and a wide range of exotic wild-caught and farm-raised fowl) are usually separated from markets selling fish or red-meat animals, but the stalls can be near each other with no physical separation. Despite the widespread availability of affordable refrigeration, many Asian people prefer live animals for fresh produce. Wet markets are widespread in Asian countries and in countries where Asian people have migrated. Live-poultry markets were the source of the H5N1 bird-influenza virus that transmitted to and killed six of 18people in Hong Kong. STARTING POINT: Yi Guan and colleagues (Science 2003; 302: 276–78) recently reported the isolation of severe acute respiratory syndrome (SARS) coronavirus (CoV) from Himalayan palm civets (Paguna larvata) in wet markets in Shenzen, southern China. These researchers also found serological evidence of infection in raccoon dogs (Nyctereutes pro-cuyoinboides). Serological evidence for SARS CoV in human beings working in these markets, taken together with the earliest cases of SARS in restaurant workers, supports the contention of a potential zoonotic origin for SARS. WHERE NEXT? Will SARS reappear? This question confronts public-health officials worldwide, particularly infectious disease personnel in those regions of the world most affected by the disease and the economic burden of SARS, including China, Taiwan, and Canada. Will the virus re-emerge from wet markets or from laboratories working with SARS CoV, or are asymptomatic infections ongoing in human beings? Similar questions can be asked about a pandemic of influenza that is probably imminent. Knowledge of the ecology of influenza in wet markets can be used as an early-warning system to detect the reappearance of SARS or pandemic influenza.

Lancet2004       CORD-19
756Development and clinical application of a rapid IgM-IgG combined antibody test for SARS-CoV-2 infection diagnosis  

The outbreak of the novel coronavirus disease (COVID‐19) quickly spread all over China and to more than 20 other countries. Although the virus (severe acute respiratory syndrome coronavirus [SARS‐Cov‐2]) nucleic acid real‐time polymerase chain reaction (PCR) test has become the standard method for diagnosis of SARS‐CoV‐2 infection, these real‐time PCR test kits have many limitations. In addition, high false‐negative rates were reported. There is an urgent need for an accurate and rapid test method to quickly identify a large number of infected patients and asymptomatic carriers to prevent virus transmission and assure timely treatment of patients. We have developed a rapid and simple point‐of‐care lateral flow immunoassay that can detect immunoglobulin M (IgM) and IgG antibodies simultaneously against SARS‐CoV‐2 virus in human blood within 15 minutes which can detect patients at different infection stages. With this test kit, we carried out clinical studies to validate its clinical efficacy uses. The clinical detection sensitivity and specificity of this test were measured using blood samples collected from 397 PCR confirmed COVID‐19 patients and 128 negative patients at eight different clinical sites. The overall testing sensitivity was 88.66% and specificity was 90.63%. In addition, we evaluated clinical diagnosis results obtained from different types of venous and fingerstick blood samples. The results indicated great detection consistency among samples from fingerstick blood, serum and plasma of venous blood. The IgM‐IgG combined assay has better utility and sensitivity compared with a single IgM or IgG test. It can be used for the rapid screening of SARS‐CoV‐2 carriers, symptomatic or asymptomatic, in hospitals, clinics, and test laboratories.

J Med Virol2020       LitCov and CORD-19
757A short, animated video to improve good COVID-19 hygiene practices: a structured summary of a study protocol for a randomized controlled trial  

OBJECTIVES: Entertainment-education (E-E) media can improve behavioral intent toward health-related practices. In the era of COVID-19, millions of people can be reached by E-E media without requiring any physical contact. We have designed a short, wordless, animated video about COVID-19 hygiene practices—such as social distancing and frequent hand washing—that can be rapidly distributed through social media channels to a global audience. The E-E video’s effectiveness, however, remains unclear. 1. Quantify people’s interest in watching a short, animated video about COVID-19 hygiene (abbreviated to CoVideo). 2. Establish the CoVideo’s effectiveness in increasing behavioural intent toward COVID-19 hygiene. 3. Establish the CoVideo’s effectiveness in improving COVID-19 hygiene knowledge. TRIAL DESIGN: The present study is a multi-site, parallel group, randomized controlled trial (RCT) comparing the effectiveness of the CoVideo against an attention placebo control (APC) video or no video. The trial has an intervention arm (CoVideo), placebo arm (APC), and control arm (no video). Nested in each trial arm is a list experiment and questionnaire survey, with the following ordering. Arm 1: the CoVideo, list experiment, and questionnaire survey. Arm 2: the APC video, list experiment, questionnaire survey, and CoVideo. Arm 3: the list experiment, questionnaire survey, and CoVideo. For each list experiment, participants will be randomized to a control or treatment group. The control group will receive a list of five items and the treatment group will receive the same five items plus one item about COVID-19 hygiene. We will use the list experiment to reduce response bias associated with socially desirable answers to COVID-19 questions. The questionnaire survey will include items about the participant’s age, sex, country of residence, highest education, and knowledge of COVID-19 spread. After completing the list experiment and questionnaire survey, participants in Arms 2 and 3 will receive the CoVideo to ensure post-trial access to treatment. PARTICIPANTS: This will be an online study setting. We will use Prolific Academic (ProA: https://www.prolific.co) to recruit participants and host our study on the Gorilla™ platform (www.gorilla.sc). To be eligible, participants must be between the age of 18 and 59 years (male, female, or other) and have current residence in the United States, the United Kingdom, Germany, Spain, Mexico, or France. Participants will be excluded from the study if they cannot speak English, German, French, or Spanish (since the instructions and survey questions will be available in these 4 languages only). INTERVENTION AND COMPARATOR: The intervention is an E-E video about COVID-19 hygiene (CoVideo). Developed by our co-author (MA) for Stanford Medicine, the CoVideo is animated with sound effects, and has no words, speech, or text. The CoVideo shows how the novel coronavirus is spread (airborne, physical contact) and summarizes the public’s response to the COVID-19 outbreak. Key components of the CoVideo are the promotion of five hygiene practices: i) social distancing and avoiding group gatherings, ii) frequently washing hands with soap and water or sanitizer, iii) cleaning surfaces at home (e.g., kitchen counters), iv) not sharing eating utensils, and v) avoidance of stockpiling essential goods (such as toilet paper and face masks). The CoVideo, which was designed for universal reach and optimized for release on social media channels, can be viewed at https://www.youtube.com/watch?v=rAj38E7vrS8. The comparators are an APC video (Arm 2) or no video (Arm 3). The APC video is similar in style to the CoVideo; it is also animated with a duration of 2.30 minutes, has sound effects but no words, speech, or text. The video message is about how small choices become actions, which become habits, which become a way of life. It is available at https://www.youtube.com/watch?v=_HEnohs6yYw. Each list experiment will have a control list as the comparator. The control list is needed to measure the prevalence of behavioral intent toward COVID-19 hygiene. MAIN OUTCOMES: This study will measure primary and secondary outcomes related to COVID-19 hygiene. By hygiene, we mean the adoption of behaviors or practices that reduce the chances of being infected or spreading COVID-19. As our primary outcome, we will measure changes in behavioral intent toward five hygiene practices: social distancing, washing hands, cleaning household surfaces, not sharing eating utensils, and not stockpiling essential goods. As a secondary outcome, we will measure knowledge about behaviors that can prevent the spread of COVID-19. RANDOMIZATION: Using a web-based randomization algorithm, Gorilla will randomly allocate participants to the intervention (CoVideo), placebo (APC), or control (no video) arm (sequence generation) at a 1:1:1 ratio. Within each trial arm, Gorilla will randomly allocate participants at a 1:1 ratio to the control or treatment group. Items in the lists will be randomly ordered to avoid order effects. The presentation order of the list experiments will also be randomized. BLINDING: Because ProA handles the interaction between the study investigators and participants, the participants will be completely anonymous to the study investigators. The outcome measures will be self-reported and submitted anonymously. All persons in the study team will be blinded to the group allocation. NUMBERS TO BE RANDOMIZED: The Gorilla algorithm will randomize 6,700 participants to each trial arm, giving a total sample size of 20,100. TRIAL STATUS: The protocol version number is 1.0 and the date is 18 May 2020. Recruitment is expected to end by 22 June 2020. Thus far, the study investigators have recruited 2,500 participants on ProA. Of these participants, 800 have completed the study on the Gorilla platform. TRIAL REGISTRATION: The study and its outcomes were registered at the German Clinical Trials Register (www.drks.de) on May 12(th), 2020, protocol number: #DRKS00021582. The study was registered before any data was collected. FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.

Trials2020       LitCov and CORD-19
758Crystal structure of SARS-CoV-2 main protease provides a basis for design of improved alpha-ketoamide inhibitors  

The COVID-19 pandemic caused by SARS-CoV-2 is a global health emergency. An attractive drug target among coronaviruses is the main protease (M(pro), 3CL(pro)), due to its essential role in processing the polyproteins that are translated from the viral RNA. We report the X-ray structures of the unliganded SARS-CoV-2 M(pro) and its complex with an α-ketoamide inhibitor. This was derived from a previously designed inhibitor but with the P3-P2 amide bond incorporated into a pyridone ring to enhance the half-life of the compound in plasma. Based on the structure, we developed the lead compound into a potent inhibitor of the SARS-CoV-2 M(pro). The pharmacokinetic characterization of the optimized inhibitor reveals a pronounced lung tropism and suitability for administration by the inhalative route.

Science2020       LitCov and CORD-19
759Managing COVID-19 within and across health systems: why we need performance intelligence to coordinate a global response  

BACKGROUND: The COVID-19 pandemic is a complex global public health crisis presenting clinical, organisational and system-wide challenges. Different research perspectives on health are needed in order to manage and monitor this crisis. Performance intelligence is an approach that emphasises the need for different research perspectives in supporting health systems’ decision-makers to determine policies based on well-informed choices. In this paper, we present the viewpoint of the Innovative Training Network for Healthcare Performance Intelligence Professionals (HealthPros) on how performance intelligence can be used during and after the COVID-19 pandemic. DISCUSSION: A lack of standardised information, paired with limited discussion and alignment between countries contribute to uncertainty in decision-making in all countries. Consequently, a plethora of different non-data-driven and uncoordinated approaches to address the outbreak are noted worldwide. Comparative health system research is needed to help countries shape their response models in social care, public health, primary care, hospital care and long-term care through the different phases of the pandemic. There is a need in each phase to compare context-specific bundles of measures where the impact on health outcomes can be modelled using targeted data and advanced statistical methods. Performance intelligence can be pursued to compare data, construct indicators and identify optimal strategies. Embracing a system perspective will allow countries to take coordinated strategic decisions while mitigating the risk of system collapse.A framework for the development and implementation of performance intelligence has been outlined by the HealthPros Network and is of pertinence. Health systems need better and more timely data to govern through a pandemic-induced transition period where tensions between care needs, demand and capacity are exceptionally high worldwide. Health systems are challenged to ensure essential levels of healthcare towards all patients, including those who need routine assistance. CONCLUSION: Performance intelligence plays an essential role as part of a broader public health strategy in guiding the decisions of health system actors on the implementation of contextualised measures to tackle COVID-19 or any future epidemic as well as their effect on the health system at large. This should be based on commonly agreed-upon standardised data and fit-for-purpose indicators, making optimal use of existing health information infrastructures. The HealthPros Network can make a meaningful contribution.

Health Res Policy Syst2020       LitCov and CORD-19
760Viruses as precipitants of asthma symptoms. I. Epidemiology  

Christopher Robin had wheezles and sneezles, they bundled him into his bed. They gave him what goes with a cold in the nose, and some more for a cold in the head. They wondered if wheezles could turn into measles, if measles would turn into mumps; They examined his chest for a rash, and the rest of his body for swellings and lumps. They sent for some doctors in sneezles and wheezles, to tell them what ought to be done. All sorts and conditions of famous physicians came hurrying round at a run. They all made a note of the state of his throat, they asked if he suffered from thirst; They asked if the sneezles came after the wheezles, or if the first sneezle came first. They said, ‘If you teazle a sneezle or wheezle, a measle may easily grow. But humour or pleazle the wheezle or sneezle, the measle will certainly go.’ They expounded the reazles for sneezles and wheezles, the manner of measles when new. They said ‘If he freezles in draughts and in breezles, then PHTHEEZLES may even ensue.’ Christopher Robin got up in the morning, the sneezles had vanished away. And the look in his eye seemed to say to the sky, ‘Now, how to amuse them today?’ A. A. Milne, Now We Are Six, 1927.

Clin Exp Allergy1992       CORD-19
761Thirty-day readmission and reoperation after surgery for spinal tumors: a National Surgical Quality Improvement Program analysis  

N/A

Neurosurg Focus2016       CORD-19
762Ebola virus disease in West Africa-the first 9 months of the epidemic and forward projections  

N/A

N Engl J Med2014       CORD-19
763Clinical evidence does not support corticosteroid treatment for 2019-nCoV lung injury  

Lancet2020       LitCov and CORD-19
764The impact of COVID-19 on the undergraduate medical curriculum  

The coronavirus pandemic has impacted medical education globally. As universities seek to deliver medical education through new methods of modalities, this continuing of education ensures the learning of the future workforce of the NHS. Novel ways of online teaching should be considered in new medical curricula development, as well as methods of delivering practical skills for medical students online.

Med Educ Online2020       LitCov and CORD-19
765Binding mechanism of coronavirus main proteinase with ligands and its implication to drug design against SARS  

In order to stimulate the development of drugs against severe acute respiratory syndrome (SARS), based on the atomic coordinates of the SARS coronavirus main proteinase determined recently [Science 13 (May) (2003) (online)], studies of docking KZ7088 (a derivative of AG7088) and the AVLQSGFR octapeptide to the enzyme were conducted. It has been observed that both the above compounds interact with the active site of the SARS enzyme through six hydrogen bonds. Also, a clear definition of the binding pocket for KZ7088 has been presented. These findings may provide a solid basis for subsite analysis and mutagenesis relative to rational design of highly selective inhibitors for therapeutic application. Meanwhile, the idea of how to develop inhibitors of the SARS enzyme based on the knowledge of its own peptide substrates (the so-called “distorted key” approach) was also briefly elucidated.

Biochem Biophys Res Commun2003       CORD-19
766Description and clinical treatment of an early outbreak of severe acute respiratory syndrome (SARS) in Guangzhou, PR China  

N/A

J Med Microbiol2003       CORD-19
767Combustion in the future: The importance of chemistry  

Combustion involves chemical reactions that are often highly exothermic. Combustion systems utilize the energy of chemical compounds released during this reactive process for transportation, to generate electric power, or to provide heat for various applications. Chemistry and combustion are interlinked in several ways. The outcome of a combustion process in terms of its energy and material balance, regarding the delivery of useful work as well as the generation of harmful emissions, depends sensitively on the molecular nature of the respective fuel. The design of efficient, low-emission combustion processes in compliance with air quality and climate goals suggests a closer inspection of the molecular properties and reactions of conventional, bio-derived, and synthetic fuels. Information about flammability, reaction intensity, and potentially hazardous combustion by-products is important also for safety considerations. Moreover, some of the compounds that serve as fuels can assume important roles in chemical energy storage and conversion. Combustion processes can furthermore be used to synthesize materials with attractive properties. A systematic understanding of the combustion behavior thus demands chemical knowledge. Desirable information includes properties of the thermodynamic states before and after the combustion reactions and relevant details about the dynamic processes that occur during the reactive transformations from the fuel and oxidizer to the products under the given boundary conditions. Combustion systems can be described, tailored, and improved by taking chemical knowledge into account. Combining theory, experiment, model development, simulation, and a systematic analysis of uncertainties enables qualitative or even quantitative predictions for many combustion situations of practical relevance. This article can highlight only a few of the numerous investigations on chemical processes for combustion and combustion-related science and applications, with a main focus on gas-phase reaction systems. It attempts to provide a snapshot of recent progress and a guide to exciting opportunities that drive such research beyond fossil combustion.

Proc Combust Inst2020       CORD-19
768Occupational health responses to COVID-19: What lessons can we learn from SARS?  

On 31 December 2019, the World Health Organization (WHO) received reports of pneumonia cases of unknown etiology in the city of Wuhan in Hubei Province, China. The agent responsible was subsequently identified as a coronavirus—SARS‐CoV‐2. The WHO declared this disease as a Public Health Emergency of International Concern at the end of January 2020. This event evoked a sense of déjà vu, as it has many similarities to the outbreak of severe acute respiratory syndrome (SARS) of 2002‐2003. Both illnesses were caused by a zoonotic novel coronavirus, both originated during winter in China and both spread rapidly all over the world. However, the case‐fatality rate of SARS (9.6%) is higher than that of COVID‐19 (<4%). Another zoonotic novel coronavirus, MERS‐CoV, was responsible for the Middle East respiratory syndrome, which had a case‐fatality rate of 34%. Our experiences in coping with the previous coronavirus outbreaks have better equipped us to face the challenges posed by COVID‐19, especially in the health care setting. Among the insights gained from the past outbreaks were: outbreaks caused by viruses are hazardous to healthcare workers; the impact of the disease extends beyond the infection; general principles of prevention and control are effective in containing the disease; the disease poses both a public health as well as an occupational health threat; and emerging infectious diseases pose a continuing threat to the world. Given the perspectives gained and lessons learnt from these past events, we should be better prepared to face the current COVID‐19 outbreak.

J Occup Health2020       LitCov and CORD-19
769Severe acute respiratory syndrome (SARS): breath-taking progress  

N/A

J Med Microbiol2003       CORD-19
770Pregnancy Outcomes Among Women With and Without SARS-CoV-2 Infection  

IMPORTANCE: Published data suggest that there are increased hospitalizations, placental abnormalities, and rare neonatal transmission among pregnant women with coronavirus disease 2019 (COVID-19). OBJECTIVES: To evaluate adverse outcomes associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in pregnancy and to describe clinical management, disease progression, hospital admission, placental abnormalities, and neonatal outcomes. DESIGN, SETTING, AND PARTICIPANTS: This observational cohort study of maternal and neonatal outcomes among delivered women with and without SARS-CoV-2 during pregnancy was conducted from March 18 through August 22, 2020, at Parkland Health and Hospital System (Dallas, Texas), a high-volume prenatal clinic system and public maternity hospital with widespread access to SARS-CoV-2 testing in outpatient, emergency department, and inpatient settings. Women were included if they were tested for SARS-CoV-2 during pregnancy and delivered. For placental analysis, the pathologist was blinded to illness severity. EXPOSURES: SARS-CoV-2 infection during pregnancy. MAIN OUTCOMES AND MEASURES: The primary outcome was a composite of preterm birth, preeclampsia with severe features, or cesarean delivery for abnormal fetal heart rate among women delivered after 20 weeks of gestation. Maternal illness severity, neonatal infection, and placental abnormalities were described. RESULTS: From March 18 through August 22, 2020, 3374 pregnant women (mean [SD] age, 27.6 [6] years) tested for SARS-CoV-2 were delivered, including 252 who tested positive for SARS-CoV-2 and 3122 who tested negative. The cohort included 2520 Hispanic (75%), 619 Black (18%), and 125 White (4%) women. There were no differences in age, parity, body mass index, or diabetes among women with or without SARS-CoV-2. SARS-CoV-2 positivity was more common among Hispanic women (230 [91%] positive vs 2290 [73%] negative; difference, 17.9%; 95% CI, 12.3%-23.5%; P < .001). There was no difference in the composite primary outcome (52 women [21%] vs 684 women [23%]; relative risk, 0.94; 95% CI, 0.73-1.21; P = .64). Early neonatal SARS-CoV-2 infection occurred in 6 of 188 tested infants (3%), primarily born to asymptomatic or mildly symptomatic women. There were no placental pathologic differences by illness severity. Maternal illness at initial presentation was asymptomatic or mild in 239 women (95%), and 6 of those women (3%) developed severe or critical illness. Fourteen women (6%) were hospitalized for the indication of COVID-19. CONCLUSIONS AND RELEVANCE: In a large, single-institution cohort study, SARS-CoV-2 infection during pregnancy was not associated with adverse pregnancy outcomes. Neonatal infection may be as high as 3% and may occur predominantly among asymptomatic or mildly symptomatic women. Placental abnormalities were not associated with disease severity, and hospitalization frequency was similar to rates among nonpregnant women.

JAMA Netw Open2020       LitCov and CORD-19
771COVID-19 CG enables SARS-CoV-2 mutation and lineage tracking by locations and dates of interest  

COVID-19 CG (covidcg.org) is an open resource for tracking SARS-CoV-2 single-nucleotide variations (SNVs), lineages, and clades using the virus genomes on the GISAID database while filtering by location, date, gene, and mutation of interest. COVID-19 CG provides significant time, labor, and cost-saving utility to projects on SARS-CoV-2 transmission, evolution, diagnostics, therapeutics, vaccines, and intervention tracking. Here, we describe case studies in which users can interrogate (1) SNVs in the SARS-CoV-2 spike receptor binding domain (RBD) across different geographical regions to inform the design and testing of therapeutics, (2) SNVs that may impact the sensitivity of commonly used diagnostic primers, and (3) the emergence of a dominant lineage harboring an S477N RBD mutation in Australia in 2020. To accelerate COVID-19 efforts, COVID-19 CG will be upgraded with new features for users to rapidly pinpoint mutations as the virus evolves throughout the pandemic and in response to therapeutic and public health interventions.

Elife2021       LitCov and CORD-19
772Facing SARS-CoV-2 Pandemic at a COVID-19 Regional Children's Hospital in Italy  

N/A

Pediatr Infect Dis J2020       LitCov and CORD-19
773Stigma and Discrimination (SAD) at the Time of the SARS-CoV-2 Pandemic  

Infectious disease control is a crucial public health issue. Although it is important to urgently perform public health measures in order to reduce the risk of spread, it could end up stigmatizing entire groups of people rather than offering control measures based on sound scientific principles. This “us” versus “them” dynamic is common in stigmatization, in general, and indicates a way in which disease stigma can be viewed as a proxy for other types of fears, especially xenophobia and general fear of outsiders. The pandemic risk associated with SARS-CoV-2 infection led us to consider, among other related issues, how stigma and discrimination remain serious barriers to care for people suspected of being infected, even more if they are assisting professions, such as health workers, employed in emergency response. The purpose of this review is to evaluate and promote the importance of psychological aspects of the stigma and social discrimination (SAD) in pandemic realities and, more specifically, nowadays, in the context of SARS-CoV-2/COVID-19. Just as it happened with HIV, HCV, tuberculosis, and Zika, stigma and discrimination undermine the social fabric compromising the ethics and principles of civilization to which each individual in entitled. Recognizing disease stigma history can give us insight into how, exactly, stigmatizing attitudes are formed, and how they are disbanded. Instead of simply blaming the ignorance of people espousing stigmatizing attitudes about certain diseases, we should try to understand precisely how these attitudes are formed so that we can intervene in their dissemination. We should also look at history to see what sorts of interventions against stigma may have worked in the past. Ongoing research into stigma should evaluate what has worked in the past, as above-mentioned, providing us with some clues as to what might work in the current pandemic emergency, to reduce devastating discrimination that keeps people from getting the care they need. We propose a systematic and historical review, in order to create a scientific and solid base for the following SAD analysis. The aim is to propose a coping strategy to face stigma and discrimination (SAD) related to SARS-CoV-2/COVID-19 pandemic outbreak, borrowing coping strategy tools and solutions from other common contagious diseases. Furthermore, our study observes how knowledge, education level, and socioeconomic status (SES) can influence perception of SARS-CoV-2/ COVID-19 risk in a digital world, based on previous research, best practices, and evidence-based research.

Int J Environ Res Public Healt2020       LitCov and CORD-19
774Effectiveness of an 8-Week Web-Based Mindfulness Virtual Community Intervention for University Students on Symptoms of Stress, Anxiety and Depression: Randomized Controlled Trial  

BACKGROUND: A student mental health crisis is increasingly acknowledged and will only intensify with the COVID-19 crisis. Given accessibility of methods with demonstrated efficacy in reducing depression and anxiety (eg, mindfulness meditation and cognitive behavioral therapy [CBT]) and limitations imposed by geographic obstructions and localized expertise, web-based alternatives have become vehicles for scaled-up delivery of benefits at modest cost. Mindfulness Virtual Community (MVC), a web-based program informed by CBT constructs and featuring online videos, discussion forums, and videoconferencing, was developed to target depression, anxiety, and experiences of excess stress among university students. OBJECTIVE: The aim of this study was to assess the effectiveness of an 8-week web-based mindfulness and CBT program in reducing symptoms of depression, anxiety, and stress (primary outcomes) and increasing mindfulness (secondary outcome) within a randomized controlled trial (RCT) with undergraduate students at a large Canadian university. METHODS: An RCT was designed to assess undergraduate students (n=160) who were randomly allocated to a web-based guided mindfulness–CBT condition (n=80) or to a waitlist control (WLC) condition (n=80). The 8-week intervention consisted of a web-based platform comprising (1) 12 video-based modules with psychoeducation on students’ preidentified life challenges and applied mindfulness practice; (2) anonymous peer-to-peer discussion forums; and (3) anonymous, group-based, professionally guided 20-minute live videoconferences. The outcomes (depression, anxiety, stress, and mindfulness) were measured via an online survey at baseline and at 8 weeks postintervention using the Patient Health Questionnaire-9 (PHQ9), the Beck Anxiety Inventory (BAI), the Perceived Stress Scale (PSS), and the Five Facets Mindfulness Questionnaire Short Form (FFMQ-SF). Analyses employed generalized estimation equation methods with AR(1) covariance structures and were adjusted for possible covariates (gender, age, country of birth, ethnicity, English as first language, paid work, unpaid work, relationship status, physical exercise, self-rated health, and access to private mental health counseling). RESULTS: Of the 159 students who provided T1 data, 32 were males and 125 were females with a mean age of 22.55 years. Participants in the MVC (n=79) and WLC (n=80) groups were similar in sociodemographic characteristics at T1 with the exception of gender and weekly hours of unpaid volunteer work. At postintervention follow-up, according to the adjusted comparisons, there were statistically significant between-group reductions in depression scores (β=–2.21, P=.01) and anxiety scores (β=–4.82, P=.006), and a significant increase in mindfulness scores (β=4.84, P=.02) compared with the WLC group. There were no statistically significant differences in perceived stress for MVC (β=.64, P=.48) compared with WLC. CONCLUSIONS: With the MVC intervention, there were significantly reduced depression and anxiety symptoms but no significant effect on perceived stress. Online mindfulness interventions can be effective in addressing common mental health conditions among postsecondary populations on a large scale, simultaneously reducing the current burden on traditional counseling services. TRIAL REGISTRATION: ISRCTN Registry ISRCTN12249616; http://www.isrctn.com/ISRCTN12249616

JMIR Ment Health2020       LitCov and CORD-19
775Laboratory preparedness for SARS-CoV-2 testing in India: Harnessing a network of Virus Research & Diagnostic Laboratories  

BACKGROUND & OBJECTIVES: An outbreak of respiratory illness of unknown aetiology was reported from Hubei province of Wuhan, People's Republic of China, in December 2019. The outbreak was attributed to a novel coronavirus (CoV), named as severe acute respiratory syndrome (SARS)-CoV-2 and the disease as COVID-19. Within one month, cases were reported from 25 countries. In view of the novel viral strain with reported high morbidity, establishing early countrywide diagnosis to detect imported cases became critical. Here we describe the role of a countrywide network of VRDLs in early diagnosis of COVID-19. METHODS: The Indian Council of Medical Research (ICMR)-National Institute of Virology (NIV), Pune, established screening as well as confirmatory assays for SARS-CoV-2. A total of 13 VRDLs were provided with the E gene screening real-time reverse transcription-polymerase chain reaction (rRT-PCR) assay. VRDLs were selected on the basis of their presence near an international airport/seaport and their past performance. The case definition for testing included all individuals with travel history to Wuhan and symptomatic individuals with travel history to other parts of China. This was later expanded to include symptomatic individuals returning from Singapore, Japan, Hong Kong, Thailand and South Korea. RESULTS: Within a week of standardization of the test at NIV, all VRDLs could initiate testing for SARS-CoV-2. Till February 29, 2020, a total of 2,913 samples were tested. This included both 654 individuals quarantined in the two camps and others fitting within the case definition. The quarantined individuals were tested twice - at days 0 and 14. All tested negative on both occasions. Only three individuals belonging to different districts in Kerala were found to be positive. INTERPRETATION & CONCLUSIONS: Sudden emergence of SARS-CoV-2 and its potential to cause a pandemic posed an unsurmountable challenge to the public health system of India. However, concerted efforts of various arms of the Government of India resulted in a well-coordinated action at each level. India has successfully demonstrated its ability to establish quick diagnosis of SARS-CoV-2 at NIV, Pune, and the testing VRDLs.

Indian J Med Res2020       LitCov and CORD-19
776The effect of control strategies to reduce social mixing on outcomes of the COVID-19 epidemic in Wuhan, China: a modelling study  

Summary Background In December, 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a novel coronavirus, emerged in Wuhan, China. Since then, the city of Wuhan has taken unprecedented measures in response to the outbreak, including extended school and workplace closures. We aimed to estimate the effects of physical distancing measures on the progression of the COVID-19 epidemic, hoping to provide some insights for the rest of the world. Methods To examine how changes in population mixing have affected outbreak progression in Wuhan, we used synthetic location-specific contact patterns in Wuhan and adapted these in the presence of school closures, extended workplace closures, and a reduction in mixing in the general community. Using these matrices and the latest estimates of the epidemiological parameters of the Wuhan outbreak, we simulated the ongoing trajectory of an outbreak in Wuhan using an age-structured susceptible-exposed-infected-removed (SEIR) model for several physical distancing measures. We fitted the latest estimates of epidemic parameters from a transmission model to data on local and internationally exported cases from Wuhan in an age-structured epidemic framework and investigated the age distribution of cases. We also simulated lifting of the control measures by allowing people to return to work in a phased-in way and looked at the effects of returning to work at different stages of the underlying outbreak (at the beginning of March or April). Findings Our projections show that physical distancing measures were most effective if the staggered return to work was at the beginning of April; this reduced the median number of infections by more than 92% (IQR 66–97) and 24% (13–90) in mid-2020 and end-2020, respectively. There are benefits to sustaining these measures until April in terms of delaying and reducing the height of the peak, median epidemic size at end-2020, and affording health-care systems more time to expand and respond. However, the modelled effects of physical distancing measures vary by the duration of infectiousness and the role school children have in the epidemic. Interpretation Restrictions on activities in Wuhan, if maintained until April, would probably help to delay the epidemic peak. Our projections suggest that premature and sudden lifting of interventions could lead to an earlier secondary peak, which could be flattened by relaxing the interventions gradually. However, there are limitations to our analysis, including large uncertainties around estimates of R 0 and the duration of infectiousness. Funding Bill & Melinda Gates Foundation, National Institute for Health Research, Wellcome Trust, and Health Data Research UK.

Lancet Public Health2020       LitCov and CORD-19
777Identification of natural compounds with antiviral activities against SARS-associated coronavirus  

More than 200 Chinese medicinal herb extracts were screened for antiviral activities against Severe Acute Respiratory Syndrome-associated coronavirus (SARS-CoV) using 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium inner salt (MTS) assay for virus-induced cytopathic effect (CPE). Four of these extracts showed moderate to potent antiviral activities against SARS-CoV with 50% effective concentration (EC(50)) ranging from 2.4 ± 0.2 to 88.2 ± 7.7 μg/ml. Out of the four, Lycoris radiata was most potent. To identify the active component, L. radiata extract was subjected to further fractionation, purification, and CPE/MTS assays. This process led to the identification of a single substance lycorine as an anti-SARS-CoV component with an EC(50) value of 15.7 ± 1.2 nM. This compound has a CC(50) value of 14980.0 ± 912.0 nM in cytotoxicity assay and a selective index (SI) greater than 900. The results suggested that four herbal extracts and the compound lycorine are candidates for the development of new anti-SARS-CoV drugs in the treatment of SARS.

Antiviral Res2005       CORD-19
778Incorporating telemedicine as part of COVID-19 outbreak response systems  

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Am J Manag Care2020       LitCov and CORD-19
779Planning for smallpox outbreaks  

Mathematical models of viral transmission and control are important tools for assessing the threat posed by deliberate release of the smallpox virus and the best means of containing an outbreak. Models must balance biological realism against limitations of knowledge, and uncertainties need to be accurately communicated to policy-makers. Smallpox poses the particular challenge that key biological, social and spatial factors affecting disease spread in contemporary populations must be elucidated largely from historical studies undertaken before disease eradication in 1979. We review the use of models in smallpox planning within the broader epidemiological context set by recent outbreaks of both novel and re-emerging pathogens.

Nature2003       CORD-19
780Presence of infectious polyadenylated RNA in the coronavirus avian bronchitis virus  

Abstract Avian infectious bronchitis virus (IBV) was radiolabeled for its nucleic acid component by growth in deembryonated chicken eggs. Purified virions of IBV have a buoyant density in linear sucrose gradients of 1.17-1.18 g/cm3 and contain approximately 4% RNA by weight. The genomic ribonucleic acid of IBV shows the following characteristic: (1) It consists of one size class of single-stranded RNA having a molecular weight of 5.5-5.7 x 108 and a sedimentation coefficient of about 48 S; (2) no evidence for subunit structure is apparent since the RNA resolves as a single species with the same electrophoretic mobility in polyacrylamide gels before and after heat denaturation; (3) at least 20–30% of the RNA molecules extracted from purified virions contain sequences of polyadenylic acid of approximately 4 S size; (4) RNA obtained from detergent-disrupted virus particles by phenol-chloroform extraction is infectious for cultures of chick embryo fibroblasts, giving rise to progeny virus which is lethal for embryonated eggs. These findings, together with the observation that IBV virions do not exhibit detectable transcriptase activity, support the conclusion that the genome of this coronavirus acts directly as a messenger RNA in eukaryotic cells.

Virology1977       CORD-19
781Critical Supply Shortages-The Need for Ventilators and Personal Protective Equipment during the Covid-19 Pandemic  

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N Engl J Med2020       LitCov and CORD-19
782An outbreak of severe acute respiratory syndrome among hospital workers in a community hospital in Hong Kong  

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Ann Intern Med2003       CORD-19
783Exploring the challenges faced by frontline workers in health and social care amid the COVID-19 pandemic: experiences of frontline workers in the English Midlands region, UK  

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J Interprof Care2020       LitCov and CORD-19
784Development and evaluation of a novel loop-mediated isothermal amplification method for rapid detection of severe acute respiratory syndrome coronavirus  

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J Clin Microbiol2004       CORD-19
785Contribution of monocytes and macrophages to the local tissue inflammation and cytokine storm in COVID-19: Lessons from SARS and MERS and potential therapeutic interventions  

The COVID-19-, SARS- and MERS-related coronaviruses share many genomic and structural similarities. However, the SARS-CoV-2 is less pathogenic than SARS-CoV and MERS-CoV. Despite some differences in the cytokine patterns, it seems that the cytokine storm plays a crucial role in the pathogenesis of COVID-19-, SARS- and MERS. Monocytes and macrophages may be infected by SARS-CoV-2 through ACE2-dependent and ACE2-independent pathways. SARS-CoV-2 can effectively suppress the anti-viral IFN response in monocytes and macrophages. Since macrophages and dendritic cells (DCs) act as antigen presenting cells (APCs), the infection of these cells by SARS-CoV-2 impairs the adaptive immune responses against the virus. Upon infection, monocytes migrate to the tissues where they become infected resident macrophages, allowing viruses to spread through all organs and tissues. The SARS-CoV-2-infected monocytes and macrophages can produce large amounts of numerous types of pro-inflammatory cytokines and chemokines, which contribute to local tissue inflammation and a dangerous systemic inflammatory response called cytokine storm. Both local tissue inflammation and the cytokine storm play a fundamental role in the development COVID-19-related complications, such as acute respiratory distress syndrome (ARDS), which is a main cause of death in COVID-19 patients. Here, we describe the monocytes and macrophage responses during severe coronavirus infections, while highlighting potential therapeutic interventions to attenuate macrophage-related inflammatory reactions in possible approaches for COVID-19 treatment.

Life Sci2020       LitCov and CORD-19
786Signals for ribosomal frameshifting in the rous sarcoma virus gag-pol region  

Abstract The gag-pol protein of Rous sarcoma virus (RSV), the precursor to the enzymes responsible for reverse transcription and integration, is expressed from two genes that lie in different translational reading frames by ribosomal frameshifting. Here, we localize the site of frameshifting and show that the frameshifting reaction is mediated by slippage of two adjacent tRNAs by a single nucleotide in the 5′ direction. The gag terminator, which immediately follows the frameshift site, is not required for frameshifting. Other suspected retroviral frameshift sites mediate frameshifting when placed at the end of RSV gag. Mutations in RSV pol also affect synthesis of the gag-pol protein in vitro. The effects of these mutations best correlate with the potential to form an RNA stem-loop structure adjacent to the frameshift site. A short sequence of RSV RNA, 147 nucleotides in length, containing the frameshift site and stem-loop structure, is sufficient to direct frameshifting in a novel genetic context.

Cell1988       CORD-19
787Clinical and immunological assessment of asymptomatic SARS-CoV-2 infections  

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Nat Med2020       LitCov and CORD-19
788Symptoms and immunoglobulin development in hospital staff exposed to a SARS-CoV-2 outbreak  

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Pediatr Allergy Immunol2020       LitCov and CORD-19
789Renin-Angiotensin-Aldosterone System Inhibitors in Patients with Covid-19  

N Engl J Med2020       LitCov and CORD-19
790Effects of chloroquine on viral infections: an old drug against today's diseases  

Chloroquine is a 9-aminoquinoline known since 1934. Apart from its well-known antimalarial effects, the drug has interesting biochemical properties that might be applied against some viral infections. Chloroquine exerts direct antiviral effects, inhibiting pH-dependent steps of the replication of several viruses including members of the flaviviruses, retroviruses, and coronaviruses. Its best-studied effects are those against HIV replication, which are being tested in clinical trials. Moreover, chloroquine has immunomodulatory effects, suppressing the production/release of tumour necrosis factor α and interleukin 6, which mediate the inflammatory complications of several viral diseases. We review the available information on the effects of chloroquine on viral infections, raising the question of whether this old drug may experience a revival in the clinical management of viral diseases such as AIDS and severe acute respiratory syndrome, which afflict mankind in the era of globalisation.

Lancet Infect Dis2003       CORD-19
791SGLT2 inhibitors for the prevention of kidney failure in patients with type 2 diabetes: a systematic review and meta-analysis  

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Lancet Diabetes Endocrinol2019       CORD-19
792The outbreak of COVID-19 coronavirus and its impact on global mental health  

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Int J Soc Psychiatry2020       LitCov and CORD-19
793Experimental infection of pigs with a new porcine enteric coronavirus, CV 777  

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Am J Vet Res1980       CORD-19
794COVID-19, Australia: Epidemiology Report 17 (Fortnightly reporting period ending 24 May 2020)  

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Commun Dis Intell (2018)2020       LitCov and CORD-19
795Tracing day-zero and forecasting the COVID-19 outbreak in Lombardy, Italy: A compartmental modelling and numerical optimization approach  

INTRODUCTION: Italy became the second epicenter of the novel coronavirus disease 2019 (COVID-19) pandemic after China, surpassing by far China’s death toll. The disease swept through Lombardy, which remained in lockdown for about two months, starting from the 8th of March. As of that day, the isolation measures taken in Lombardy were extended to the entire country. Here, assuming that effectively there was one case “zero” that introduced the virus to the region, we provide estimates for: (a) the day-zero of the outbreak in Lombardy, Italy; (b) the actual number of asymptomatic infected cases in the total population until March 8; (c) the basic (R(0))and the effective reproduction number (R(e)) based on the estimation of the actual number of infected cases. To demonstrate the efficiency of the model and approach, we also provide a tentative forecast two months ahead of time, i.e. until May 4, the date on which relaxation of the measures commenced, on the basis of the COVID-19 Community Mobility Reports released by Google on March 29. METHODS: To deal with the uncertainty in the number of the actual asymptomatic infected cases in the total population Volpert et al. (2020), we address a modified compartmental Susceptible/ Exposed/ Infectious Asymptomatic/ Infected Symptomatic/ Recovered/ Dead (SEIIRD) model with two compartments of infectious persons: one modelling the cases in the population that are asymptomatic or experience very mild symptoms and another modelling the infected cases with mild to severe symptoms. The parameters of the model corresponding to the recovery period, the time from the onset of symptoms to death and the time from exposure to the time that an individual starts to be infectious, have been set as reported from clinical studies on COVID-19. For the estimation of the day-zero of the outbreak in Lombardy, as well as of the “effective” per-day transmission rate for which no clinical data are available, we have used the proposed SEIIRD simulator to fit the numbers of new daily cases from February 21 to the 8th of March. This was accomplished by solving a mixed-integer optimization problem. Based on the computed parameters, we also provide an estimation of the basic reproduction number R(0) and the evolution of the effective reproduction number R(e). To examine the efficiency of the model and approach, we ran the simulator to “forecast” the epidemic two months ahead of time, i.e. from March 8 to May 4. For this purpose, we considered the reduction in mobility in Lombardy as released on March 29 by Google COVID-19 Community Mobility Reports, and the effects of social distancing and of the very strict measures taken by the government on March 20 and March 21, 2020. RESULTS: Based on the proposed methodological procedure, we estimated that the expected day-zero was January 14 (min-max rage: January 5 to January 23, interquartile range: January 11 to January 18). The actual cumulative number of asymptomatic infected cases in the total population in Lombardy on March 8 was of the order of 15 times the confirmed cumulative number of infected cases, while the expected value of the basic reproduction number R(0) was found to be 4.53 (min-max range: 4.40- 4.65). On May 4, the date on which relaxation of the measures commenced the effective reproduction number was found to be 0.987 (interquartiles: 0.857, 1.133). The model approximated adequately two months ahead of time the evolution of reported cases of infected until May 4, the day on which the phase I of the relaxation of measures was implemented over all of Italy. Furthermore the model predicted that until May 4, around 20% of the population in Lombardy has recovered (interquartile range: ∼10% to ∼30%).

PLoS One2020       LitCov and CORD-19
796A phase II, single-center, double-blind, randomized placebo-controlled trial to explore the efficacy and safety of intravenous melatonin in patients with COVID-19 admitted to the intensive care unit (MelCOVID study): a structured summary of a study protocol for a randomized controlled trial  

OBJECTIVES: • Primary objective: to evaluate the effect of intravenous melatonin (IVM) on mortality in adult patients admitted to the intensive care unit (ICU) with COVID-19. • Secondary objectives: ◦ To evaluate the effect of IVM on ICU length of stay. ◦ To evaluate the effect of IVM on the length of mechanical ventilation (MV). ◦ To evaluate if the use of IVM is associated with an increase in the number of ventilator-free days. ◦ To evaluate if the use of IVM is associated with a reduced number of failing organs as determined by the sequential organ failure assessment (SOFA) scale. ◦ To evaluate if the use of IVM is associated with a reduction of the frequency and severity of COVID-19-associated thromboembolic phenomena. ◦ To evaluate if the use of IVM is associated with a decreased systemic inflammatory response assessed by plasma levels of ferritin, D-dimer, C-reactive protein, procalcitonin and interleukin-6. ◦ To evaluate if the use of IVM is associated with an improvement in hematologic parameters. ◦ To evaluate if the use of IVM is associated with an improvement in biochemical parameters. ◦ To evaluate if the use of IVM is associated with an improvement in blood gas analysis parameters. ◦ To evaluate adverse events during the 28 day study period. TRIAL DESIGN: Phase II, single center, double-blind, placebo-controlled randomized trial with a two-arm parallel group design and 2:1 allocation ratio. PARTICIPANTS: Only critically ill adult patients that fulfill all of the inclusion criteria and none of the exclusion criteria will be included. The study will be conducted in a mixed ICU of a publicly funded tertiary referral center in Madrid, Spain with a 30-bed capacity and 1100 admissions per year. • Inclusion criteria: ◦ Patient, family member or legal guardian has provided written Informed Consent. ◦ Age ε 18 years. ◦ Confirmed SARS-CoV-2 infection with compatible symptoms AND a positive RT-PCR. ◦ Admission to the ICU with acute hypoxemic respiratory failure attributed to SARS-CoV-2 infection. ◦ ICU length of stay of less than 7 days prior to randomization with or without MV and without signs of improvement in respiratory failure (MURRAY score at randomization greater or equal to the MURRAY score at ICU admission). • Exclusion criteria: ◦ Participant in a different COVID-19 study in which the study drug is under clinical development and hasn’t been previously authorized for commercialization. ◦ Liver enzymes > 5 times the upper normal range. ◦ Chronic kidney disease with GFR < 30 mL/min/1.73 m(2) (stage 4 or greater) or need for hemodialysis. ◦ Pregnancy. A pregnancy test will be performed on every woman younger than 55 years of age prior to inclusion. ◦ Terminal surgical or medical illness. ◦ Autoimmune disease. ◦ Any patient condition that can prevent the study procedures to be carried out at the treating physician’s judgement. INTERVENTION AND COMPARATOR: All patients will receive standard-of-care treatment according to the current institutional protocols. In addition, patients will be randomized in a 2:1 ratio to receive: • Experimental group (12 patients): 7 days of 5 mg per Kg of actual body weight per day of intravenous melatonin every 6 hours. Maximum daily dose 500 mg per day. • Control group (6 patients): 7 days of 5 mg per Kg of actual body weight per day of intravenous identically-looking placebo every 6 hours. After 3 days of treatment, 3 intensive care physicians will evaluate the participant and decide whether or not to complete the treatment based on their clinical assessment: • If objective or subjective signs of improvement or no worsening of the general clinical condition, respiratory failure, inflammatory state or multi-organ failure are observed, the participant will continue the treatment until completion. • If an adverse effect or clinical impairment is observed that is objectively or subjectively attributable to the study drug the treatment will be stopped. MAIN OUTCOME: Mortality in each study group represented in frequency and time-to-event at day 28 after randomization RANDOMIZATION: The randomization sequence was created using SAS version 9.4 statistical software (programmed and validated macros) with a 2:1 allocation. No randomization seed was pre-specified. The randomization seed was generated using the time on the computer where the program was executed. BLINDING (MASKING): Participants, caregivers and study groups will be blinded to arm allocation. NUMBERS TO BE RANDOMIZED (SAMPLE SIZE): A total of 18 patients will be randomized in this trial: 12 to the experimental arm and 6 to the control arm. TRIAL STATUS: Protocol version 2.0, June 5(th) 2020. Trial status: recruitment not started. The first patient is expected to be recruited in October 2020. The last patient is anticipated to be recruited in August 2021. TRIAL REGISTRATION: EU Clinical Trials Register. Date of trial registration: 10 July 2020. URL: https://www.clinicaltrialsregister.eu/ctr-search/trial/2020-001808-42/ES FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest of expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.

Trials2020       LitCov and CORD-19
797Adoptive transfer of EAE-like lesions from rats with coronavirus induced demyelinating encephalomyelitis  

Viruses have been found to induce inflammatory demyelinating lesions in central nervous system (CNS) tissue of both animal and man, either by natural infections or after vaccination(1,2). At least two different pathogenic mechanisms have been proposed for these changes, a cytopathic viral infection of oligodendroglia cells with subsequent cell death, and a host immune reaction against virus and brain antigens. We now report the occurrence of cell-mediated immune reactions against basic myelin proteins in the course of coronavirus infections in Lewis rats. Infection of rats with the murine coronavirus JHM leads to demyelinating encephalomyelitis developing several weeks to months post-infection(3–7). Lymphocytes from these diseased Lewis rats can be restimulated with basic myelin protein (BMP) and adoptive transfer of these cells leads to lesions resembling those of experimental allergic encephalomyelitis (EAE) in recipients, which can be accompanied by a mild clinical disease. This model demonstrates that a virus infection in CNS tissue is capable of initiating an autoimmune response which may be of pathogenic importance.

Nature1983       CORD-19
798Digital Inequality During a Pandemic: Quantitative Study of Differences in COVID-19-Related Internet Uses and Outcomes Among the General Population  

BACKGROUND: The World Health Organization considers coronavirus disease (COVID-19) to be a public emergency threatening global health. During the crisis, the public’s need for web-based information and communication is a subject of focus. Digital inequality research has shown that internet access is not evenly distributed among the general population. OBJECTIVE: The aim of this study was to provide a timely understanding of how different people use the internet to meet their information and communication needs and the outcomes they gain from their internet use in relation to the COVID-19 pandemic. We also sought to reveal the extent to which gender, age, personality, health, literacy, education, economic and social resources, internet attitude, material access, internet access, and internet skills remain important factors in obtaining internet outcomes after people engage in the corresponding uses. METHODS: We used a web-based survey to draw upon a sample collected in the Netherlands. We obtained a dataset with 1733 respondents older than 18 years. RESULTS: Men are more likely to engage in COVID-19–related communication uses. Age is positively related to COVID-19–related information uses and negatively related to information and communication outcomes. Agreeableness is negatively related to both outcomes and to information uses. Neuroticism is positively related to both uses and to communication outcomes. Conscientiousness is not related to any of the uses or outcomes. Introversion is negatively related to communication outcomes. Finally, openness relates positively to all information uses and to both outcomes. Physical health has negative relationships with both outcomes. Health perception contributes positively to information uses and both outcomes. Traditional literacy has a positive relationship with information uses and both outcomes. Education has a positive relationship with information and communication uses. Economic and social resources played no roles. Internet attitude is positively related to information uses and outcomes but negatively related to communication uses and outcomes. Material access and internet access contributed to all uses and outcomes. Finally, several of the indicators and outcomes became insignificant after accounting for engagement in internet uses. CONCLUSIONS: Digital inequality is a major concern among national and international scholars and policy makers. This contribution aimed to provide a broader understanding in the case of a major health pandemic by using the ongoing COVID-19 crisis as a context for empirical work. Several groups of people were identified as vulnerable, such as older people, less educated people, and people with physical health problems, low literacy levels, or low levels of internet skills. Generally, people who are already relatively advantaged are more likely to use the information and communication opportunities provided by the internet to their benefit in a health pandemic, while less advantaged individuals are less likely to benefit. Therefore, the COVID-19 crisis is also enforcing existing inequalities.

J Med Internet Res2020       LitCov and CORD-19
799Severe acute respiratory distress syndrome (SARS): a critical care perspective  

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Crit Care Med2003       CORD-19
800Viral load dynamics and disease severity in patients infected with SARS-CoV-2 in Zhejiang province, China, January-March 2020: retrospective cohort study  

OBJECTIVE: To evaluate viral loads at different stages of disease progression in patients infected with the 2019 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) during the first four months of the epidemic in Zhejiang province, China. DESIGN: Retrospective cohort study. SETTING: A designated hospital for patients with covid-19 in Zhejiang province, China. PARTICIPANTS: 96 consecutively admitted patients with laboratory confirmed SARS-CoV-2 infection: 22 with mild disease and 74 with severe disease. Data were collected from 19 January 2020 to 20 March 2020. MAIN OUTCOME MEASURES: Ribonucleic acid (RNA) viral load measured in respiratory, stool, serum, and urine samples. Cycle threshold values, a measure of nucleic acid concentration, were plotted onto the standard curve constructed on the basis of the standard product. Epidemiological, clinical, and laboratory characteristics and treatment and outcomes data were obtained through data collection forms from electronic medical records, and the relation between clinical data and disease severity was analysed. RESULTS: 3497 respiratory, stool, serum, and urine samples were collected from patients after admission and evaluated for SARS-CoV-2 RNA viral load. Infection was confirmed in all patients by testing sputum and saliva samples. RNA was detected in the stool of 55 (59%) patients and in the serum of 39 (41%) patients. The urine sample from one patient was positive for SARS-CoV-2. The median duration of virus in stool (22 days, interquartile range 17-31 days) was significantly longer than in respiratory (18 days, 13-29 days; P=0.02) and serum samples (16 days, 11-21 days; P<0.001). The median duration of virus in the respiratory samples of patients with severe disease (21 days, 14-30 days) was significantly longer than in patients with mild disease (14 days, 10-21 days; P=0.04). In the mild group, the viral loads peaked in respiratory samples in the second week from disease onset, whereas viral load continued to be high during the third week in the severe group. Virus duration was longer in patients older than 60 years and in male patients. CONCLUSION: The duration of SARS-CoV-2 is significantly longer in stool samples than in respiratory and serum samples, highlighting the need to strengthen the management of stool samples in the prevention and control of the epidemic, and the virus persists longer with higher load and peaks later in the respiratory tissue of patients with severe disease.

BMJ2020       LitCov and CORD-19

(1) COVID-19 Open Research Dataset (CORD-19). 2020. Version 2022-06-02. Retrieved from https://ai2-semanticscholar-cord-19.s3-us-west-2.amazonaws.com/historical_releases.html. Accessed 2022-06-05. doi:10.5281/zenodo.3715506
(2) Chen Q, Allot A, & Lu Z. (2020) Keep up with the latest coronavirus research, Nature 579:193 and Chen Q, Allot A, Lu Z. LitCovid: an open database of COVID-19 literature. Nucleic Acids Research. 2020. (version 2023-01-10)
(3) Currently tweets of June 23rd to June 29th 2022 have been considered.

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